The application describes the five-year Mentored Patient-Oriented Research Career Development program (K-23) of Helen Lavretsky, M.D., devoted to the development of necessary research skills to conduct intervention studies of geriatric depression, as well as to study underlying mechanisms of variable treatment response. During the award period, the candidate proposes to engage in an organized program of interdisciplinary training and supervised research under the sponsorship of Dr. Anand Kumar enabling her to conduct methodologically sound intervention studies in depressed geriatric patients and become an independent clinical scientist. The existing evidence indicates that an antidepressant response may be less favorable in patients age 70 and older than in younger patients. Accelerated treatment may be particularly beneficial in this group of patients, which are prone to increased frailty and suicide. Chronic medical conditions frequently co-occur with depression in the elderly and may alter disease course and treatment response. Different treatment strategies of depression in these patients may be warranted. There is presently a lack of prospective controlled augmentation antidepressant trials in patients at least 70 years old. The main goal of the proposed project, a randomized, double-blind, placebo-controlled clinical trial of a low-dose methylphenidate (MPH) augmentation of citalopram is to determine whether the addition of MPH to citalopram would increase efficacy and decrease the time to antidepressant response in depressed elderly outpatients age 70 and older. The characteristics of treatment response (speed, completeness, and durability) will be assessed. The PI will also investigate the role of medical burden, cerebrovascular disease, and cognitive impairment documented on magnetic resonance imaging (MRI) in the mechanisms of variability of treatment response. The significance of MRI signal hyperintensities for treatment response will be explored as well. The proposed project will serve as a methodological template for future studies of geriatric depression. Dr. Lavretsky will also improve her skills in the MRI methodology, image analysis, and neuropsychological assessment of geriatric depressed patients. She will spend time in training at the NIMH-sponsored Late-Life Mood Disorders Intervention Center learning the methodology of conducting clinical trials (University of Pittsburgh). Additional coursework and supervision will include reviewing clinical psychopharmacology and experimental therapeutics, biostatistics, clinical trials research design and conduct, bioethics of the responsible conduct of research with the emphasis on clinical trials. With the additional skills and experience acquired during the Award period, Dr. Lavretsky will be well prepared to undertake independent investigations.